tert-butyl 3-(1H-5-indazolylamino)-1-piperidinecarboxylate | 353547-86-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: tert-butyl 3-(1H-5-indazolylamino)-1-piperidinecarboxylate
• 英文别名: 5-(1-tert-butoxycarbonyl-piperidin-3-ylamino)-indazole；tert-butyl 3-(1H-indazol-5-ylamino)piperidine-1-carboxylate
• CAS: 353547-86-1
• 化学式: C₁₇H₂₄N₄O₂
• 分子量: 316.403
• InChiKey: QBRBSIGRWPWRQW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  70.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 3-(1H-5-indazolylamino)-1-piperidinecarboxylate 在 4-二甲氨基吡啶 、 硼烷四氢呋喃络合物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 氯仿 、 乙腈 为溶剂， 反应 3.0h， 生成 N-[1-(1H-3-pyrrolylmethyl)-3-piperidyl]-N-(1H-5-indazolyl)amine
  参考文献：
  名称：

  Design and synthesis of Rho kinase inhibitors (II)

  摘要：

  In a previous study, we identified several structurally unrelated scaffolds of the Rho kinase inhibitor using pharmacophore information obtained from the results of a high-throughput screening and structural information from a homology model of Rho kinase. 1H-Indazole is one of the candidate scaffolds on which a new series of potent Rho kinase inhibitors could be developed. In this study, the detailed structure-activity relationship of 1H-indazole analogues was studied. During this study, we found that the cell-free enzyme inhibitory potential of Rho kinase inhibitors having the 1H-indazole scaffold did not necessarily correlate with their inhibitory potential toward the chemotaxis of cultured cells. The choice of the linker substructure was shown to be an important factor for the 1H-indazole analogues to inhibit the chemotaxis of cells. Optimization of the 1H-indazole inhibitors with respect to the in vitro inhibition of monocyte chemotaxis induced by MCP-1 was carried out. The inhibitory potential was improved both in the cell-free enzyme assay and in the chemotaxis assay. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.09.052
• 作为产物：
  描述：

  N-BOC-3-羟基哌啶 在 吡啶硼烷 、 三甲基氨基磺酸 、 溶剂黄146 、 二甲基亚砜 、 三乙胺 作用下， 以 甲醇 为溶剂， 反应 36.0h， 生成 tert-butyl 3-(1H-5-indazolylamino)-1-piperidinecarboxylate
  参考文献：
  名称：

  Design and synthesis of Rho kinase inhibitors (II)

  摘要：

  In a previous study, we identified several structurally unrelated scaffolds of the Rho kinase inhibitor using pharmacophore information obtained from the results of a high-throughput screening and structural information from a homology model of Rho kinase. 1H-Indazole is one of the candidate scaffolds on which a new series of potent Rho kinase inhibitors could be developed. In this study, the detailed structure-activity relationship of 1H-indazole analogues was studied. During this study, we found that the cell-free enzyme inhibitory potential of Rho kinase inhibitors having the 1H-indazole scaffold did not necessarily correlate with their inhibitory potential toward the chemotaxis of cultured cells. The choice of the linker substructure was shown to be an important factor for the 1H-indazole analogues to inhibit the chemotaxis of cells. Optimization of the 1H-indazole inhibitors with respect to the in vitro inhibition of monocyte chemotaxis induced by MCP-1 was carried out. The inhibitory potential was improved both in the cell-free enzyme assay and in the chemotaxis assay. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.09.052

文献信息

• Design, Synthesis, and Biological Evaluation of an Orally Bioavailable, Potent, and Selective ROCK2 Inhibitor for Psoriasis Treatment
  作者：Yun Huang、Chu-Ru Mao、Yijie Lou、Shuai Zhan、Zhe Chen、Wanjing Ding、Zhongjun Ma

  DOI：10.1021/acs.jmedchem.3c01297

  日期：2023.11.23

  significant therapeutic obstacle. This study centers on rho-associated coiled-coil-containing kinase2 (ROCK2) as an advantageous target for treating psoriasis and identifies five potent and selective ROCK2 inhibitors (A31–35). Notably, A32–35 outperform KD025 in ROCK2/ROCK1 selectivity by up to 216-fold. Among these candidates, A31 emerged as an exceedingly promising molecule, showcasing remarkable inhibitory

  牛皮癣是一种流行的慢性皮肤病，仍然是一个重大的治疗障碍。这项研究以 rho 相关卷曲螺旋激酶 2 (ROCK2) 为中心，将其作为治疗银屑病的有利靶点，并确定了五种有效且选择性的 ROCK2 抑制剂 ( A31 – 35 )。值得注意的是， A32 – 35在 ROCK2/ROCK1 选择性方面优于 KD025 高达 216 倍。在这些候选药物中， A31成为一种非常有前途的分子，表现出显着的抑制效力 (IC 50 = 3.7 ± 0.8 nM)、19 倍的 ROCK2/ROCK1 选择性和良好的药代动力学。结合模式研究的见解进一步强调了与 P 环上的 Phe103 相互作用在确定 ROCK1 和 ROCK2 之间的选择性方面的关键作用。在咪喹莫特诱导的银屑病样小鼠模型中，口服A31通过靶向 IL-23/Th17 轴显着改善症状。基于这些令人信服的发现， A31被选为一种非常有前途的化合物
• WO2006/135383
  申请人：——

  公开号：——

  公开（公告）日：——
• US7217722B2
  申请人：——

  公开号：US7217722B2

  公开（公告）日：2007-05-15
• [EN] INDAZOLES<br/>[FR] INDAZOLES
  申请人：MYRIAD GENETICS INC

  公开号：WO2006135383A2

  公开（公告）日：2006-12-21

  [EN] Methods and pharmaceutical compositions for treating and/or delaying the onset of viral infection are provided. The pharmaceutical compositions include compounds having an indazole core. Additionally, the compositions can be used to treat cardiovascular disorders and cancer.
  [FR] L'invention concerne des procédés et compositions pharmaceutiques permettant de traiter et/ou retarder le début d'une infection virale. Ces compositions pharmaceutiques comprennent des composés possédant un noyau d'indazole. En outre, ces compositions peuvent être utilisées pour traiter des troubles cardio-vasculaires et le cancer.
• Design and synthesis of Rho kinase inhibitors (II)
  作者：Masayuki Iwakubo、Atsuya Takami、Yuji Okada、Takehisa Kawata、Yoshimichi Tagami、Hiroshi Ohashi、Motoko Sato、Terumi Sugiyama、Kayoko Fukushima、Hiroshi Iijima

  DOI：10.1016/j.bmc.2006.09.052

  日期：2007.1.1

  In a previous study, we identified several structurally unrelated scaffolds of the Rho kinase inhibitor using pharmacophore information obtained from the results of a high-throughput screening and structural information from a homology model of Rho kinase. 1H-Indazole is one of the candidate scaffolds on which a new series of potent Rho kinase inhibitors could be developed. In this study, the detailed structure-activity relationship of 1H-indazole analogues was studied. During this study, we found that the cell-free enzyme inhibitory potential of Rho kinase inhibitors having the 1H-indazole scaffold did not necessarily correlate with their inhibitory potential toward the chemotaxis of cultured cells. The choice of the linker substructure was shown to be an important factor for the 1H-indazole analogues to inhibit the chemotaxis of cells. Optimization of the 1H-indazole inhibitors with respect to the in vitro inhibition of monocyte chemotaxis induced by MCP-1 was carried out. The inhibitory potential was improved both in the cell-free enzyme assay and in the chemotaxis assay. (c) 2006 Elsevier Ltd. All rights reserved.